Yu Hongluan, Fan Cuiqin, Yang Lejin, Yu Shuyan, Song Qiqi, Wang Peng, Mao Xueqin
Department of Psychiatry, Qilu Hospital of Shandong University, Jinan, China.
Department of Physiology, Shandong University, School of Medicine, Jinan, China.
Cell Physiol Biochem. 2018;48(6):2470-2482. doi: 10.1159/000492684. Epub 2018 Aug 17.
BACKGROUND/AIMS: Ginsenoside Rg1 has been demonstrated to exhibit neuroprotective effects in various studies. This study aimed to investigate the neuronal mechanisms underlying the neuroprotective and antidepressant-like effects of ginsenoside Rg1 in a rat model of depression.
Chronic unpredictable mild stress was used to induce depression-like behaviors in rats. Transmission electron microscopy was used to observe neuronal synapses within the basolateral amygdala (BLA). The expression of microRNA (miR)-134 in the BLA was verified by real-time quantitative PCR. Finally, the synaptic plasticity-associated proteins CAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were detected by immunoblotting.
Results showed that chronic stress effectively induced depression-like behaviors in rats, which were associated with significant ultrastructural changes within BLA neurons. Moreover, chronic stress decreased the expression of miR-134 in the BLA, which was accompanied by decreased phosphorylation of CREB and decreased expression of BDNF. Remarkably, chronic administration of ginsenoside Rg1 (40 mg/kg, i.p., 5 weeks) significantly ameliorated the neuronal structural abnormalities and biochemical changes induced by chronic stress, as well as preventing depression-like behaviors in these rats.
Results suggested that ginsenoside Rg1 may exhibit neuroprotection and antidepressant-like effects by activating the CREB-BDNF system within the BLA in this rat model of depression. Amelioration of depression-like behaviors by ginsenoside Rg1 appears to involve modulation of the synapse-associated factor miR-134 within the BLA. Therefore, these findings demonstrate some of the neuronal mechanisms associated with depression and the therapeutic potential of ginsenoside Rg1 for use in the treatment of depression in clinical trials.
背景/目的：在多项研究中已证实人参皂苷Rg1具有神经保护作用。本研究旨在探讨人参皂苷Rg1在大鼠抑郁模型中发挥神经保护和抗抑郁样作用的神经元机制。
采用慢性不可预测性轻度应激诱导大鼠出现抑郁样行为。运用透射电子显微镜观察基底外侧杏仁核（BLA）内的神经元突触。通过实时定量PCR验证BLA中微小RNA（miR）-134的表达。最后，采用免疫印迹法检测突触可塑性相关蛋白环磷酸腺苷反应元件结合蛋白（CREB）和脑源性神经营养因子（BDNF）。
结果显示，慢性应激可有效诱导大鼠出现抑郁样行为，这与BLA神经元内显著的超微结构变化有关。此外，慢性应激降低了BLA中miR-134的表达，同时伴有CREB磷酸化水平降低和BDNF表达减少。值得注意的是，慢性给予人参皂苷Rg1（40mg/kg，腹腔注射，共5周）可显著改善慢性应激诱导的神经元结构异常和生化变化，并预防这些大鼠出现抑郁样行为。
结果表明，在该大鼠抑郁模型中，人参皂苷Rg1可能通过激活BLA内的CREB-BDNF系统发挥神经保护和抗抑郁样作用。人参皂苷Rg1改善抑郁样行为似乎涉及对BLA内突触相关因子miR-134的调节。因此，这些研究结果揭示了一些与抑郁相关的神经元机制以及人参皂苷Rg1在临床试验中用于治疗抑郁的潜在治疗价值。
